High-fat diet without excess calories induces metabolic disorders and enhances atherosclerosis in rabbits

Abstract

Objective Excess intake of a high-fat diet (HFD) is associated with obesity and metabolic syndrome, which are major risk factors for cardiovascular disease. However, it is unclear whether consumption of an HFD at a normal calorific range would be detrimental to metabolism or affect the development of atherosclerosis. Here, we tested the hypothesis that consumption of a normal-calorie HFD would impair lipid metabolism, insulin sensitivity, and blood pressure. Methods and results Rabbits fed with an HFD containing either 3% (15% kcal from fat) or 10% (25.8% kcal from fat) coconut oil were compared with control rabbits fed with a standard chow diet (9.3% kcal from fat). All rabbits consumed an equal amount of calories of their respective food. However, HFD feeding induced marked metabolic disorders including increased plasma levels of free fatty acids, insulin resistance, and hypertension compared with control rabbits. Metabolic disorders were more pronounced in 10%-HFD-fed rabbits than 3%-HFD-fed rabbits. To examine whether these disorders affected the development of atherosclerosis, two HFD groups were further fed with a diet containing 0.3% cholesterol for another 18 weeks. We found that 10%-HFD group showed a prominent accumulation of adipose tissue and developed 2-fold greater aortic atherosclerosis than 3%-HFD group. Conclusions These results suggest that consuming an HFD containing even a normal number of calories can cause insulin resistance, hypertension, and adipose accumulation even without obesity. High amounts of fat in diets apparently accelerate the development of atherosclerosis.